The project is designed to test whether the presentation of varicella zoster virus (VZV) antigens in a particulate, polyvalent form as hybrid Ty virus-like particles (Ty-VLPs) results in enhanced immune responses as compared to those induced by the currently available live virus vaccine. In order to further augment the immune response and to facilitate administration, a variety of adjuvants and immunization routes will be investigated. The ultimate goal of the study is to develop a cheap, safe, stable, efficacious and easily administered subunit VZV vaccine candidate for clinical evaluation. VZV is the etiologic agent of chickenpox and shingles, and is a member of the herpes virus family. VZV is highly infectious and is spread by airborne droplets. In immunocompromised children a severe, progressive chickenpox may develop which can lead to a high risk of mortality. Worldwide estimates of infection are 57 million cases of chickenpox in children and 3 million in adults per year, with 5 million cases of shingles. An effective mass childhood vaccination program could substantially reduce the annual incidence of chickenpox. However, the current live, attenuated vaccine is unsuitable for such a programme due to concerns over batch-to-batch variability, re-infection, re-activation and long-term efficacy. The experimental plan is to characterize both systemic and mucosal immune responses to VZV following immunization with hybrid VZV:Ty-VLPs containing fragments of the VZV glycoprotein gpI and the nucleoprotein complex p32/p36 using parenteral and/or mucosal routes with a range of different adjuvants. Immunogenicity will be measured in terms of the neutralizing antibody and cell-mediated immunity induced. These studies will test whether VZV:Ty-VLPs can induce immunity at levels superior to the current VZV vaccine or monomeric, recombinant proteins, and whether this immunity can be elicited when the immunogens are administered by mucosal routes. VZV represents an ideal disease model for the herpes virus family and there is an urgent need for an efficacious subunit vaccine which may be used in both children and adults. We anticipate that this research plan will define a vaccine strategy, using VZV, that is applicable to many diseases.